The special session on liver cirrhosis with severe infection was concluded

Speech by Professor Xu Xiaoyuan

      Esther Fages Contel, Director of East Asia Affairs of Kilefour, mentioned that hundreds of millions of people worldwide are affected by liver cirrhosis, and nearly 50% of patients with liver cirrhosis are in China. Liver cirrhosis and its related complications seriously affect the quality of life of patients, and bring heavy burden to patients, medical institutions and society. This meeting brought together many experts and scholars at home and abroad, believing that this is a very good opportunity to support the treatment progress of cirrhosis and its related complications in China.

Speech by Esther Fages Contel

      In the academic part of "International Frontier", Professor Javier Fernandez from Spain elaborated on the treatment progress of spontaneous bacterial peritonitis (SBP). The incidence rate of bacterial infection in cirrhosis is 32-39%, and the incidence rate in ICU is as high as 59%. SBP is the most common type of bacterial infection in cirrhosis. Many factors are related to the occurrence of bacterial infection in liver cirrhosis, including liver cirrhosis related immune dysfunction, intestinal barrier dysfunction, intestinal flora, clinical factors and genetic factors, among which the imbalance of flora caused by excessive growth of intestinal bacteria is particularly important. In the case of dysbacteriosis, intestinal mucosal permeability increases, leading to bacterial translocation. The translocated bacteria and bacterial products activate the innate immune system through Toll like receptors and inflammatory bodies, producing a large number of inflammatory cytokines, and leading to subsequent liver damage.

      According to a global survey data conducted by the International Ascites Club (ICA) in 2019, the prevalence rate of multidrug resistant bacteria in patients with liver cirrhosis is 34%. The prevalence rate of multidrug resistant bacteria varies significantly in different regions, with the highest prevalence rate in Asia. Delayed or inadequate initial empirical antibiotic treatment can lead to increased mortality. The empirical antibiotic treatment strategy should not only consider the type of infection (SBP, urinary tract infection, pneumonia or cellulitis) and source of infection (community acquired infection or hospital infection) of patients with liver cirrhosis, but also adapt to local conditions and follow the principle of descending the ladder.

      Albumin is an effective drug for the treatment and prevention of SBP in liver cirrhosis, which is mainly related to the mechanism that albumin can ultimately improve circulatory dysfunction by expanding blood volume and improving endothelial cell dysfunction. A RCT study data showed that albumin (1.5g/kg body weight on the first day, 1.0g/kg body weight on the third day) combined with antibiotic treatment effectively prevented hepatorenal syndrome in SBP patients, and improved short-term survival rate. ANSWER research data shows that long-term use of albumin can prevent the occurrence of SBP. Albumin can prevent nosocomial infection in patients with cirrhosis and non SBP infection.

      The dosage of albumin also has an important influence on the treatment of patients with liver cirrhosis and hypoalbuminemia. The preliminary data of PRECIOSA study showed that the circulatory dysfunction and systemic inflammation in patients with liver cirrhosis were extremely unstable, and the plasma renin level and interleukin-6 level had a strong and reversible peak. High dose albumin (1.5g/kg body weight per week for 12 weeks) can normalize the serum albumin level and stabilize the circulatory dysfunction and systemic inflammation in patients with liver cirrhosis.

Lecture by Professor Javier Fernandez

      Professor Joan Claria shared the anti-inflammatory effect of albumin in the treatment of liver cirrhosis. He said that the data from PRECIOSA preliminary study and INFECIR-2 study suggest that albumin infusion can be used as a new treatment to reduce systemic inflammatory response in patients with acute decompensated cirrhosis (AD).

      In vitro studies and animal studies have confirmed that albumin is internalized into leukocyte vesicles under the guidance of FcRn in neonates. It blocks the expression and release of cytokines induced by CpG DNA by interfering with the signal pathway of cytosine guanine phosphate dideoxynucleotide motif (CpG DNA) - Toll like receptor 9 (TLR9, It comes from the unique molecular structure of albumin. Albumin can effectively reduce the release of cytokines from leukocytes without damaging the immune defense function of leukocytes.

      Albumin also protects tissues from inflammatory damage caused by cytokines. In the in vitro precision dry section (PCLS) test and in vitro primary hepatocyte culture test, it was confirmed that albumin can reduce the release of mitochondrial cytochrome C and the activity of cysteine proteinase 3 by inhibiting the leakage of cathepsin B in lysosome body, thus reducing the release of mitochondrial cytochrome C and the activity of cysteine proteinase 3 α （TNF α） Mediated hepatocyte injury has a protective effect, which is also independent of albumin clearance.

      The latest study to observe the effect of human serum albumin on the blood lipid profile of patients with AD liver cirrhosis shows that the content of proinflammatory lipid mediators in the albumin of patients with AD liver cirrhosis is lower than that of healthy subjects. After administration of exogenous human serum albumin, the level of prostaglandin like inflammatory mediators in patients decreased, and albumin induced the expression of 15 lipoxygenase, as well as the release of 15 HETE, 17 HDHA and other lipid mediators with anti-inflammatory and inflammatory regression effects.

Lecture by Professor Joan Claria

      In the academic part of "Voice of China", Professor Zhang Wenhong introduced in detail the impact of COVID-19 and the vaccination of COVID-19 vaccine in the special group of patients with liver diseases. Professor Zhang Wenhong pointed out that the mortality of patients with liver cirrhosis complicated by COVID-19 infection was significantly higher than that of patients without liver cirrhosis. In the outbreak of Omicron infection in Shanghai in March this year, except for the elderly (>80 years old), the combination of basic liver disease was one of the risk factors for Omicron infection to become serious/critical.

      The data from the study on the safety and immunogenicity of inactivated COVID-19 vaccine vaccination in people with liver cirrhosis suggest that although the safety of inactivated vaccine has obtained satisfactory results, its immunogenicity is lower than that of healthy people, especially in patients with decompensated liver cirrhosis with Child Pugh score of B and C, whose immune reactivity is lower after COVID-19 vaccination. In the population with chronic hepatitis B virus infection, primary liver cancer and liver transplantation, the study on the safety and immunogenicity of COVID-19 vaccination has obtained similar results.

      With the emergence of new COVID-19 variants and the reduction of antibodies after vaccination, the third dose of COVID-19 enhanced vaccine is now considered an effective strategy. COVID-19 fortified vaccine has been proved to have good safety and immunogenicity in healthy people. Now, the multicenter study on the safety and immunogenicity of COVID-19 enhanced vaccine (NMCID-CHESS 2201) has also been carried out among people with chronic liver disease.

Professor Zhang Wenhong gives lectures

      During the symposium, Professor Liu Jianxiang from the First Hospital of Peking University asked questions about the optimal serum albumin level for liver cirrhosis patients to supplement albumin. Professor Xu Jinghang from the First Hospital of Peking University asked about the treatment of liver cirrhosis with fungal infection by albumin. Professor Yang Li from West China Hospital of Sichuan University raised questions about the use of albumin in patients with liver cirrhosis complicated by SBP or pulmonary infection who had double infection. Professor Huang Zuxiong, Meng Chao Hepatobiliary Hospital of Fujian Medical University, said that there was a big difference in the amount of albumin used in the treatment of SBP patients with liver cirrhosis at home and abroad. Especially in China's basic hospitals, low dose albumin (10-20g/day) was often used for 7-10 days. The effective albumin concentration in patients with liver cirrhosis was significantly reduced. Therefore, for patients with liver cirrhosis infection combined with hypoalbuminemia, the adjustment of antibiotic dose should also be taken into account when conducting anti infection treatment.

      Professor Javier Fernandez believes that when improving hypoalbuminemia in patients with decompensated cirrhosis by infusion of human serum albumin, it is necessary to at least correct the patient's serum albumin level to the normal range. Low serum albumin level will affect the efficacy of antibiotic treatment in anti infection treatment, but albumin alone cannot be used as a means of anti infection treatment. Fungal infection of liver cirrhosis is not as common as bacterial infection. At present, there is no research on albumin treatment in this kind of population. The most important thing is to give appropriate antibacterial treatment at an early stage. Considering the risk of pulmonary edema in patients with liver cirrhosis complicated with pulmonary infection, albumin infusion will not be carried out. Neither liver cirrhosis with SBP nor lung infection was treated with immunoglobulin. Immunoglobulin will only be considered in patients with chronic acute liver failure undergoing plasma exchange.

      Professor Gao Yanhang from the First Hospital of Jilin University said that the infection rate of patients with alcoholic liver disease was more than three times that of normal people. Alcoholic liver disease with infection and hypoalbuminemia will further lead to acute decompensation and chronic acute liver failure. In the treatment of alcoholic liver disease with infection, albumin can play a certain anti-inflammatory role, but the prevention of infection needs more attention from clinicians, and more indicators and methods for early diagnosis of infection need to be explored.

      Professor Rao Huiying, People's Hospital of Peking University, said that when diagnosing SBP in patients with liver cirrhosis, it is necessary to actively conduct albumin infusion. In patients with hepatorenal syndrome, acute renal injury or high serum bilirubin, albumin infusion can bring greater benefits to patients. For patients with decompensated liver cirrhosis complicated with obstinate ascites, albumin infusion is also required actively when a large amount of ascites is discharged through abdominal puncture. The specific scheme for long-term use of albumin in patients with liver cirrhosis in China, such as the dose and frequency of albumin, and other indicators guiding albumin infusion besides the level of serum albumin, needs further exploration.

      Professor Ma Xiong, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University, said that albumin is a crucial drug in the treatment of patients with decompensated liver cirrhosis. Through this meeting, we expanded our understanding of white protein, and learned that albumin not only improves colloid osmotic pressure, but also has other rich physiological functions such as immune regulation, anti-inflammatory, etc.

      Professor Han Tao from the People's Hospital of Nankai University said that the prevention of infection in patients with liver cirrhosis was crucial, but the dose and course of treatment of albumin still needed further exploration. Professor Wu Biao of Hainan Provincial People's Hospital said that albumin can significantly benefit patients in the treatment of liver cirrhosis complications and improve the prognosis of liver cirrhosis patients, which is supported by clear evidence based medical evidence.

      Finally, Professor Zhang Wenhong, a special guest, said that patients with liver cirrhosis were a group worth exploring, and looked forward to more opportunities for cooperative research in the future. Professor Javier Fernandez expects to explore more indications and mechanisms of albumin use in the future, and the latest clinical research results on long-term use of albumin will be published in the next year. Professor Joan Claria said that the redox form of albumin would have an important impact on the therapeutic effect of clinical patients. Professor Jia Jidong, the chairman of the conference, summarized the wonderful contents of the conference, again emphasized the benefits of albumin in the treatment of patients with decompensated cirrhosis, and understood that albumin has anti-inflammatory effects in addition to maintaining colloid osmotic pressure, which is helpful to further guide the rational use of albumin in clinical practice, and also hopes that there will be more opportunities for communication and cooperation in the future.